Seasonal Influenza, Vaccine
Conditions
Keywords
influenza, vaccine
Brief summary
Evaluation of the safety of Trivalent Subunit Influenza Vaccine Produced either in Mammalian Cell Culture or in embryonated Hen Eggs in subjects 18 years of age and above with and without underlying medical conditions and evaluation of the immunogenicity in a subset of subjects with underlying medical conditions, compared to an egg-based vaccine in a post marketing setting.
Interventions
BIOLOGICALCell-derived influenza vaccine
1 dose of 0.5 mL in the deltoid region of the non-dominant arm
BIOLOGICALEgg-derived influenza vaccine
1 dose of 0.5 mL in the deltoid region of the non-dominant arm
Sponsors
Novartis Vaccines
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Subjects 18 years of age and above, mentally competent, willing and able to give informed consent prior to study entry; 2. Able to comply with all study procedures and requirements.
Exclusion criteria
1. History of any anaphylaxis, serious vaccine reactions, or hypersensitivity to any vaccine component; 2. Fatal prognosis of an underlying medical condition (\<12 months life expectancy); 3. History of Guillain-Barre syndrome; 4. Bleeding diathesis or receiving anticoagulants of the coumarin type; 5. Hospitalization or residence in a nursing care facility; 6. Planned to receive seasonal influenza vaccine outside of this study; 7. Receipt of another vaccine within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrollment in this study; 8. Fever (defined as axillary temperature ≥38.0°C) or any acute illness within 3 days prior to study vaccination; 9. Receipt of another investigational agent within 30 days prior to enrollment in the study or before completion of the safety follow-up period in another study, whichever is longer, and unwilling to refuse participation in another clinical study through the end safety follow up period of the study; 10. Any condition, which, in the opinion of the investigator, might prevent the subject from participation or interfere with the evaluation of the study objectives; 11. Females who were pregnant or nursing (breastfeeding) mothers, or females of childbearing potential who were sexually active and had not used or did not plan to use acceptable birth control measures during the first 3 weeks after vaccination. Oral, injected or implanted hormonal contraceptive, diaphragm or condom with spermicidal agent or intrauterine device were considered acceptable forms of birth control.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | From Day 1 up to and including Day 7 post-vaccination | Safety was assessed as the number of all subjects who reported at least one sign of reactogenicity after one vaccination of egg-derived (TIV) or cell culture-derived (cTIV) influenza virus vaccine from Day 1 through Day 7 post-vaccination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | From Day 1 through Day 7 post-vaccination | Analysis was performed on a subset of safety population which included the adults (≥18 to ≤60 years) and elderly (≥61 years) with underlying medical conditions. |
| Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | Before vaccination (Day 1) and three weeks after vaccination (Day 22) | Immunogenicity was measured as the percentage of adults (≥18 to ≤60 years) and elderly (≥61 years) achieving HI titers ≥40 at baseline (Day 1) and three weeks (Day 22) after one vaccination of TIV or cTIV for each of three vaccine strains, evaluated using hemagglutination inhibition (HI) egg-derived antigen assay. This criterion is met according to European (CHMP) guideline if the percentage of subjects achieving HI titers ≥40 is \>70% (≥18 to ≤60 years), or \>60% (≥61 years). |
| Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | From Day 1 through Day 7 post-vaccination | Analysis was performed on a subset of safety population which included the healthy adults (≥18 to ≤60 years) and elderly (≥61 years). |
| Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | Before vaccination (Day 1) and three weeks after vaccination (Day 22) | Immunogenicity was measured as HI geometric mean titers (GMTs) of subjects with underlying conditions, directed against each of three vaccine strains at baseline (Day 1) and three weeks after vaccination (Day 22) in adults (≥18 to ≤60 years) and elderly (≥61 years). |
| Geometric Mean Ratio of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | Three weeks post-vaccination (Day 22) | Immunogenicity was measured as the geometric mean ratio (GMR), calculated as the ratio of postvaccination to prevaccination HI GMTs for each of the three strains, three weeks after one vaccination (Day 22) of TIV or cTIV. CHMP criteria is considered fulfilled for each of the three strains if the geometric mean increase GMR (Day 22/Day 1) in HI antibody titer is \>2.5 (≥18 to ≤60 years) or \>2.0 (≥61 Years). |
| Percentages Of Subjects Who Achieved Seroconversion Or Significant Increase In HI Titers After One Vaccination of TIV or cTIV | Three weeks post-vaccination (Day 22) | Seroconversion or significant increase in HI titer as per CHMP criteria for each of the three strains is defined as the percentage of subjects with a prevaccination HI titer \<10 to a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, a ≥4-fold increase in postvaccination HI antibody titer. According to the CHMP criteria, the percentage of subjects achieving seroconversion/significant increase should be \>40% (≥18 to ≤60 years) or \>30% (≥61 years). |
Countries
Germany
Participant flow
Recruitment details
Subjects were enrolled at 17 centres in Germany.
Pre-assignment details
All enrolled subjects were included in the trial.
Participants by arm
| Arm | Count |
|---|---|
| Egg-derived Vaccine (TIV) Subjects received one vaccination of a egg-derived trivalent influenza virus vaccine | 396 |
| Cell Culture-derived Vaccine (cTIV) Subjects received one vaccination of a cell-derived trivalent influenza virus vaccine | 1,002 |
| Total | 1,398 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative reason | 0 | 5 |
| Overall Study | Death | 2 | 1 |
| Overall Study | Lost to Follow-up | 4 | 10 |
| Overall Study | Missing primary reason | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Total | Egg-derived Vaccine (TIV) | Cell Culture-derived Vaccine (cTIV) |
|---|---|---|---|
| Age, Continuous | 48.3 years STANDARD_DEVIATION 16.6 | 47.6 years STANDARD_DEVIATION 17.3 | 48.7 years STANDARD_DEVIATION 16.3 |
| Sex: Female, Male Female | 739 Participants | 206 Participants | 533 Participants |
| Sex: Female, Male Male | 659 Participants | 190 Participants | 469 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 204 / 396 | 568 / 1,001 |
| serious Total, serious adverse events | 10 / 396 | 20 / 1,001 |
Outcome results
Primary
Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV
Safety was assessed as the number of all subjects who reported at least one sign of reactogenicity after one vaccination of egg-derived (TIV) or cell culture-derived (cTIV) influenza virus vaccine from Day 1 through Day 7 post-vaccination.
Time frame: From Day 1 up to and including Day 7 post-vaccination
Population: Analysis was performed on the safety dataset, i.e. all subjects in the exposed set who provided post-baseline safety data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Any reaction - Missing | 1 Subjects |
| TIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Any reaction - None | 204 Subjects |
| TIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Any reaction - Other than severe | 186 Subjects |
| TIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Any reaction - Severe | 5 Subjects |
| TIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Local reaction - Missing | 5 Subjects |
| TIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Local reaction - None | 274 Subjects |
| TIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Local reaction - Other than severe | 117 Subjects |
| TIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Local reaction - Severe | 0 Subjects |
| TIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Systemic reaction - Missing | 1 Subjects |
| TIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Systemic reaction - None | 250 Subjects |
| TIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Systemic reaction - Other than severe | 140 Subjects |
| TIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Systemic reaction - Severe | 5 Subjects |
| cTIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Systemic reaction - Other than severe | 369 Subjects |
| cTIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Any reaction - Missing | 2 Subjects |
| cTIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Local reaction - Other than severe | 325 Subjects |
| cTIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Any reaction - None | 488 Subjects |
| cTIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Systemic reaction - None | 616 Subjects |
| cTIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Any reaction - Other than severe | 495 Subjects |
| cTIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Local reaction - Severe | 5 Subjects |
| cTIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Any reaction - Severe | 16 Subjects |
| cTIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Systemic reaction - Severe | 14 Subjects |
| cTIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Local reaction - Missing | 17 Subjects |
| cTIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Systemic reaction - Missing | 2 Subjects |
| cTIV (Adults) | Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV | Local reaction - None | 654 Subjects |
Secondary
Geometric Mean Ratio of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV
Immunogenicity was measured as the geometric mean ratio (GMR), calculated as the ratio of postvaccination to prevaccination HI GMTs for each of the three strains, three weeks after one vaccination (Day 22) of TIV or cTIV. CHMP criteria is considered fulfilled for each of the three strains if the geometric mean increase GMR (Day 22/Day 1) in HI antibody titer is \>2.5 (≥18 to ≤60 years) or \>2.0 (≥61 Years).
Time frame: Three weeks post-vaccination (Day 22)
Population: Analysis was performed on the immunogenicity subset of adults and elderly with underlying medical conditions.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| TIV (Adults) | Geometric Mean Ratio of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H1N1 | 9.65 Ratio |
| TIV (Adults) | Geometric Mean Ratio of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | B | 5.88 Ratio |
| TIV (Adults) | Geometric Mean Ratio of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H3N2 | 7.35 Ratio |
| cTIV (Adults) | Geometric Mean Ratio of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H1N1 | 9 Ratio |
| cTIV (Adults) | Geometric Mean Ratio of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | B | 3.57 Ratio |
| cTIV (Adults) | Geometric Mean Ratio of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H3N2 | 5.32 Ratio |
| TIV (Elderly) | Geometric Mean Ratio of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H3N2 | 3.12 Ratio |
| TIV (Elderly) | Geometric Mean Ratio of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H1N1 | 6.96 Ratio |
| TIV (Elderly) | Geometric Mean Ratio of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | B | 2.17 Ratio |
| cTIV (Elderly) | Geometric Mean Ratio of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H1N1 | 5.35 Ratio |
| cTIV (Elderly) | Geometric Mean Ratio of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | B | 1.92 Ratio |
| cTIV (Elderly) | Geometric Mean Ratio of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H3N2 | 3.58 Ratio |
Secondary
Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV
Immunogenicity was measured as HI geometric mean titers (GMTs) of subjects with underlying conditions, directed against each of three vaccine strains at baseline (Day 1) and three weeks after vaccination (Day 22) in adults (≥18 to ≤60 years) and elderly (≥61 years).
Time frame: Before vaccination (Day 1) and three weeks after vaccination (Day 22)
Population: Analysis was performed on the immunogenicity subset of adults and elderly with underlying medical conditions.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| TIV (Adults) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | B (Day 22) | 55 Titers |
| TIV (Adults) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H3N2 (Day 22) | 224 Titers |
| TIV (Adults) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H1N1 (Day 1) | 37 Titers |
| TIV (Adults) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H3N2 (Day 1) | 31 Titers |
| TIV (Adults) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | B (Day 1) | 9.35 Titers |
| TIV (Adults) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H1N1 (Day 22) | 354 Titers |
| cTIV (Adults) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | B (Day 1) | 11 Titers |
| cTIV (Adults) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | B (Day 22) | 39 Titers |
| cTIV (Adults) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H1N1 (Day 22) | 308 Titers |
| cTIV (Adults) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H1N1 (Day 1) | 34 Titers |
| cTIV (Adults) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H3N2 (Day 1) | 29 Titers |
| cTIV (Adults) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H3N2 (Day 22) | 156 Titers |
| TIV (Elderly) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H1N1 (Day 22) | 132 Titers |
| TIV (Elderly) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | B (Day 1) | 20 Titers |
| TIV (Elderly) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H3N2 (Day 22) | 174 Titers |
| TIV (Elderly) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H1N1 (Day 1) | 19 Titers |
| TIV (Elderly) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | B (Day 22) | 43 Titers |
| TIV (Elderly) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H3N2 (Day 1) | 56 Titers |
| cTIV (Elderly) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | B (Day 22) | 26 Titers |
| cTIV (Elderly) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H1N1 (Day 1) | 29 Titers |
| cTIV (Elderly) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H1N1 (Day 22) | 158 Titers |
| cTIV (Elderly) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H3N2 (Day 22) | 145 Titers |
| cTIV (Elderly) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | B (Day 1) | 14 Titers |
| cTIV (Elderly) | Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV | A/H3N2 (Day 1) | 41 Titers |
Secondary
Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV
Analysis was performed on a subset of safety population which included the adults (≥18 to ≤60 years) and elderly (≥61 years) with underlying medical conditions.
Time frame: From Day 1 through Day 7 post-vaccination
Population: Analysis was done on the subset of safety population which included the adults and elderly with underlying medical conditions.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TIV (Adults) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Malaise (N=220,484,98,263) | 27 Subjects |
| TIV (Adults) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Fever (≥38 °C) | 1 Subjects |
| TIV (Adults) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Arthralgia (N=220,484,98,263) | 10 Subjects |
| TIV (Adults) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Myalgia (N=220,484,98,263) | 32 Subjects |
| TIV (Adults) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Fatigue (N=220,484,98,263) | 37 Subjects |
| TIV (Adults) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Chills (N=220,484,98,263) | 5 Subjects |
| TIV (Adults) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Pain (N=220,484,98,263) | 77 Subjects |
| TIV (Adults) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Sweating (N=220,484,98,263) | 12 Subjects |
| TIV (Adults) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Headache (N=220,484,98,263) | 40 Subjects |
| cTIV (Adults) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Fatigue (N=220,484,98,263) | 102 Subjects |
| cTIV (Adults) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Pain (N=220,484,98,263) | 189 Subjects |
| cTIV (Adults) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Chills (N=220,484,98,263) | 15 Subjects |
| cTIV (Adults) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Malaise (N=220,484,98,263) | 51 Subjects |
| cTIV (Adults) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Myalgia (N=220,484,98,263) | 80 Subjects |
| cTIV (Adults) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Arthralgia (N=220,484,98,263) | 35 Subjects |
| cTIV (Adults) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Headache (N=220,484,98,263) | 94 Subjects |
| cTIV (Adults) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Sweating (N=220,484,98,263) | 33 Subjects |
| cTIV (Adults) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Fever (≥38 °C) | 5 Subjects |
| TIV (Elderly) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Malaise (N=220,484,98,263) | 5 Subjects |
| TIV (Elderly) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Arthralgia (N=220,484,98,263) | 8 Subjects |
| TIV (Elderly) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Headache (N=220,484,98,263) | 15 Subjects |
| TIV (Elderly) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Chills (N=220,484,98,263) | 3 Subjects |
| TIV (Elderly) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Fever (≥38 °C) | 2 Subjects |
| TIV (Elderly) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Sweating (N=220,484,98,263) | 6 Subjects |
| TIV (Elderly) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Fatigue (N=220,484,98,263) | 14 Subjects |
| TIV (Elderly) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Myalgia (N=220,484,98,263) | 15 Subjects |
| TIV (Elderly) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Pain (N=220,484,98,263) | 15 Subjects |
| cTIV (Elderly) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Fatigue (N=220,484,98,263) | 33 Subjects |
| cTIV (Elderly) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Sweating (N=220,484,98,263) | 10 Subjects |
| cTIV (Elderly) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Arthralgia (N=220,484,98,263) | 14 Subjects |
| cTIV (Elderly) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Chills (N=220,484,98,263) | 9 Subjects |
| cTIV (Elderly) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Fever (≥38 °C) | 1 Subjects |
| cTIV (Elderly) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Pain (N=220,484,98,263) | 32 Subjects |
| cTIV (Elderly) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Headache (N=220,484,98,263) | 40 Subjects |
| cTIV (Elderly) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Myalgia (N=220,484,98,263) | 23 Subjects |
| cTIV (Elderly) | Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV | Malaise (N=220,484,98,263) | 13 Subjects |
Secondary
Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV
Analysis was performed on a subset of safety population which included the healthy adults (≥18 to ≤60 years) and elderly (≥61 years).
Time frame: From Day 1 through Day 7 post-vaccination
Population: Analysis was done on a subset of safety population (i.e. all subjects in the exposed population who provide postvaccination safety data) which included the healthy adults and elderly.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TIV (Adults) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Sweating (N=66,226,7,11) | 1 Subjects |
| TIV (Adults) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Headache (N=66,226,7,11) | 14 Subjects |
| TIV (Adults) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Fever (≥38 °C) | 0 Subjects |
| TIV (Adults) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Myalgia (N=66,226,7,11) | 10 Subjects |
| TIV (Adults) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Malaise (N=66,226,7,11) | 7 Subjects |
| TIV (Adults) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Chills (N=66,226,7,11) | 1 Subjects |
| TIV (Adults) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Fatigue (N=66,226,7,11) | 11 Subjects |
| TIV (Adults) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Arthralgia (N=66,226,7,11) | 2 Subjects |
| TIV (Adults) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Pain (N=66,226,7,11) | 24 Subjects |
| cTIV (Adults) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Arthralgia (N=66,226,7,11) | 13 Subjects |
| cTIV (Adults) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Sweating (N=66,226,7,11) | 13 Subjects |
| cTIV (Adults) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Headache (N=66,226,7,11) | 47 Subjects |
| cTIV (Adults) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Chills (N=66,226,7,11) | 10 Subjects |
| cTIV (Adults) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Pain (N=66,226,7,11) | 107 Subjects |
| cTIV (Adults) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Malaise (N=66,226,7,11) | 25 Subjects |
| cTIV (Adults) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Fever (≥38 °C) | 2 Subjects |
| cTIV (Adults) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Fatigue (N=66,226,7,11) | 49 Subjects |
| cTIV (Adults) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Myalgia (N=66,226,7,11) | 46 Subjects |
| TIV (Elderly) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Arthralgia (N=66,226,7,11) | 0 Subjects |
| TIV (Elderly) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Pain (N=66,226,7,11) | 1 Subjects |
| TIV (Elderly) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Chills (N=66,226,7,11) | 0 Subjects |
| TIV (Elderly) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Malaise (N=66,226,7,11) | 0 Subjects |
| TIV (Elderly) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Myalgia (N=66,226,7,11) | 0 Subjects |
| TIV (Elderly) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Headache (N=66,226,7,11) | 0 Subjects |
| TIV (Elderly) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Sweating (N=66,226,7,11) | 2 Subjects |
| TIV (Elderly) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Fatigue (N=66,226,7,11) | 1 Subjects |
| TIV (Elderly) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Fever (≥38 °C) | 0 Subjects |
| cTIV (Elderly) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Sweating (N=66,226,7,11) | 0 Subjects |
| cTIV (Elderly) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Myalgia (N=66,226,7,11) | 0 Subjects |
| cTIV (Elderly) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Malaise (N=66,226,7,11) | 0 Subjects |
| cTIV (Elderly) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Fever (≥38 °C) | 0 Subjects |
| cTIV (Elderly) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Fatigue (N=66,226,7,11) | 1 Subjects |
| cTIV (Elderly) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Chills (N=66,226,7,11) | 0 Subjects |
| cTIV (Elderly) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Headache (N=66,226,7,11) | 2 Subjects |
| cTIV (Elderly) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Arthralgia (N=66,226,7,11) | 1 Subjects |
| cTIV (Elderly) | Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV | Pain (N=66,226,7,11) | 2 Subjects |
Secondary
Percentages Of Subjects Who Achieved Seroconversion Or Significant Increase In HI Titers After One Vaccination of TIV or cTIV
Seroconversion or significant increase in HI titer as per CHMP criteria for each of the three strains is defined as the percentage of subjects with a prevaccination HI titer \<10 to a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, a ≥4-fold increase in postvaccination HI antibody titer. According to the CHMP criteria, the percentage of subjects achieving seroconversion/significant increase should be \>40% (≥18 to ≤60 years) or \>30% (≥61 years).
Time frame: Three weeks post-vaccination (Day 22)
Population: Analysis was performed on the immunogenicity subset of adults and elderly with underlying medical conditions.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TIV (Adults) | Percentages Of Subjects Who Achieved Seroconversion Or Significant Increase In HI Titers After One Vaccination of TIV or cTIV | A/H1N1 | 64 Percentages of Subjects |
| TIV (Adults) | Percentages Of Subjects Who Achieved Seroconversion Or Significant Increase In HI Titers After One Vaccination of TIV or cTIV | B | 55 Percentages of Subjects |
| TIV (Adults) | Percentages Of Subjects Who Achieved Seroconversion Or Significant Increase In HI Titers After One Vaccination of TIV or cTIV | A/H3N2 | 62 Percentages of Subjects |
| cTIV (Adults) | Percentages Of Subjects Who Achieved Seroconversion Or Significant Increase In HI Titers After One Vaccination of TIV or cTIV | A/H1N1 | 65 Percentages of Subjects |
| cTIV (Adults) | Percentages Of Subjects Who Achieved Seroconversion Or Significant Increase In HI Titers After One Vaccination of TIV or cTIV | B | 41 Percentages of Subjects |
| cTIV (Adults) | Percentages Of Subjects Who Achieved Seroconversion Or Significant Increase In HI Titers After One Vaccination of TIV or cTIV | A/H3N2 | 56 Percentages of Subjects |
| TIV (Elderly) | Percentages Of Subjects Who Achieved Seroconversion Or Significant Increase In HI Titers After One Vaccination of TIV or cTIV | A/H3N2 | 40 Percentages of Subjects |
| TIV (Elderly) | Percentages Of Subjects Who Achieved Seroconversion Or Significant Increase In HI Titers After One Vaccination of TIV or cTIV | A/H1N1 | 72 Percentages of Subjects |
| TIV (Elderly) | Percentages Of Subjects Who Achieved Seroconversion Or Significant Increase In HI Titers After One Vaccination of TIV or cTIV | B | 24 Percentages of Subjects |
| cTIV (Elderly) | Percentages Of Subjects Who Achieved Seroconversion Or Significant Increase In HI Titers After One Vaccination of TIV or cTIV | A/H1N1 | 60 Percentages of Subjects |
| cTIV (Elderly) | Percentages Of Subjects Who Achieved Seroconversion Or Significant Increase In HI Titers After One Vaccination of TIV or cTIV | B | 20 Percentages of Subjects |
| cTIV (Elderly) | Percentages Of Subjects Who Achieved Seroconversion Or Significant Increase In HI Titers After One Vaccination of TIV or cTIV | A/H3N2 | 40 Percentages of Subjects |
Secondary
Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV
Immunogenicity was measured as the percentage of adults (≥18 to ≤60 years) and elderly (≥61 years) achieving HI titers ≥40 at baseline (Day 1) and three weeks (Day 22) after one vaccination of TIV or cTIV for each of three vaccine strains, evaluated using hemagglutination inhibition (HI) egg-derived antigen assay. This criterion is met according to European (CHMP) guideline if the percentage of subjects achieving HI titers ≥40 is \>70% (≥18 to ≤60 years), or \>60% (≥61 years).
Time frame: Before vaccination (Day 1) and three weeks after vaccination (Day 22)
Population: Analysis was performed on the immunogenicity subset of adults and elderly with underlying medical conditions (full analysis set \[FAS\]: all enrolled subjects who received a study vaccine and provided one evaluable serum sample before and after baseline)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TIV (Adults) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | A/H1N1 (Day 1) | 56 Percentages of Subjects |
| TIV (Adults) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | A/H1N1 (Day 22) | 98 Percentages of Subjects |
| TIV (Adults) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | A/H3N2 (Day 1) | 53 Percentages of Subjects |
| TIV (Adults) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | A/H3N2 (Day 22) | 97 Percentages of Subjects |
| TIV (Adults) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | B (Day 1) | 14 Percentages of Subjects |
| TIV (Adults) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | B (Day 22) | 77 Percentages of Subjects |
| cTIV (Adults) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | B (Day 22) | 63 Percentages of Subjects |
| cTIV (Adults) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | A/H3N2 (Day 22) | 87 Percentages of Subjects |
| cTIV (Adults) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | A/H1N1 (Day 1) | 53 Percentages of Subjects |
| cTIV (Adults) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | A/H3N2 (Day 1) | 46 Percentages of Subjects |
| cTIV (Adults) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | A/H1N1 (Day 22) | 95 Percentages of Subjects |
| cTIV (Adults) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | B (Day 1) | 16 Percentages of Subjects |
| TIV (Elderly) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | A/H1N1 (Day 22) | 96 Percentages of Subjects |
| TIV (Elderly) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | A/H3N2 (Day 1) | 80 Percentages of Subjects |
| TIV (Elderly) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | A/H3N2 (Day 22) | 100 Percentages of Subjects |
| TIV (Elderly) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | B (Day 22) | 68 Percentages of Subjects |
| TIV (Elderly) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | B (Day 1) | 40 Percentages of Subjects |
| TIV (Elderly) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | A/H1N1 (Day 1) | 40 Percentages of Subjects |
| cTIV (Elderly) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | B (Day 1) | 28 Percentages of Subjects |
| cTIV (Elderly) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | B (Day 22) | 48 Percentages of Subjects |
| cTIV (Elderly) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | A/H1N1 (Day 22) | 100 Percentages of Subjects |
| cTIV (Elderly) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | A/H3N2 (Day 22) | 88 Percentages of Subjects |
| cTIV (Elderly) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | A/H1N1 (Day 1) | 56 Percentages of Subjects |
| cTIV (Elderly) | Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV | A/H3N2 (Day 1) | 64 Percentages of Subjects |